Aims: Genome-wide association studies (GWAS) have been conducted in multifactorial diseases such as autoimmune diseases, and more than 1000 disease susceptibility variants have been identified. However, GWAS only indicates the presence of disease-causing variants within a region. The effects of the accumulation of these variants on the functions of cells and tissues involved in disease states must be clarified. This study aims to integrate public GWAS data and expression quantitative trait loci (eQTL) and splicing QTL (sQTL) analyses to elucidate the pathogenesis of various multifactorial diseases through a comprehensive analysis of functional variants.

Methods: [DRA016393 / DRA016394 / DDRA016395 / RA018714] Total RNAs from Lymphoblastoid Cell line (LCL) samples were used for Iso-seq and RNA-seq analyses [DRA016285] Twenty-nine immune cell subsets were isolated from peripheral blood mononuclear cells using the 14-color cell sorter BD FACSAria Fusion. Total RNA was extracted, followed by polyA selection and cDNA library preparation using the SMART-seq v4 Ultra Low Input RNA Kit and SQK-LSK109 for cDNA library preparation. For flow cytometry staining panels, the definitions of the Human Immunology Project were followed. Neutrophils were recovered with EasySep Direct Human Neutrophil Isolation Kits or MACSxpress Neutrophil Isolation Kits human. The generated cDNA was sequenced by Flongle Flow Cell (long-read system).

Targets: [DRA016393 / DRA016394 / DDRA016395 / RA018714] Samples with and without interferon (IFNa2) stimulation were obtained from LCL samples derived from the 1000 Genomes Registry. [DRA016285] 29 immune cell types isolated from peripheral blood cells collected from a 42-year-old healthy individual